Parasitic diseases are the most widespread of all the major human diseases. Effective treatment is nonexistent for many of them, and most of the available drugs have been shown to have mutagenic, cytotoxic, and carcinogenic activities. Recently it has become increasingly apparent that many reactive intermediates of xenobiotics are free radicals. The formation of free radicals, including oxygen-derived radicals, may lead to extensive cellular damage. The consequences of radical-initiated reactions may be the immediate death of the cells or may be more subtle and delayed as evidenced by the development of neoplasms. In a study of Trypanosoma cruzi (the agent of Chagas' disease), crystal violet, a triarylmethane dye widely used by blood banks to eliminate transmission of Chagas' disease by transfusion, was found to undergo a one-electron reduction to produce a carbon-centered free radical. Both radical formation and the trypanocidal action of crystal violet, were enhanced by light. The photodynamic action of rose bengal on T. cruzi has also been established. These observations may have important chemoprophylactic implications, since illumination of blood to be transfused may result in a better therapeutic ratio. The free radical intermediates (superoxide anion, hydroxyl radical) generated by human polymorphonuclear leukocytes in the presence of antibody-coated T. cruzi were identified by ESR spectroscopy. These radicals may play an important role in host resistance and/or pathogenesis of Chagas' disease. The ability of Tritrichomonas foetus (the agent of trichomoniasis in cattle) hydrogenosomal and cytosolic fractions to generate metronidazole and nitrofuran anion radicals was established. These results support the role of air oxidation as a detoxification reaction for the metronidazole anion radical and the involvement of a ferredoxin in its formation. On the other hand, redox cycling of nitrofurans, with formation of high steady state concentrations of oxygen-derived radicals, might be of toxicological significance.